Synthesis
The general procedure for the synthesis of 6-bromo-5-nitroquinoline from 6-bromoquinoline was as follows: 6-bromoquinoline (0.190 g, 0.932 mmol) was dissolved in 4 mL of concentrated sulfuric acid and cooled to -5 °C in a salt-ice bath. An acid mixture consisting of concentrated sulfuric acid (1.5 mL) and concentrated nitric acid (1.5 mL) was prepared and cooled to -5°C. The 6-bromoquinoline solution was kept cooled at 0°C. The mixed acid was slowly added dropwise to the 6-bromoquinoline solution under magnetic stirring using a Pasteur pipette, and the dropwise process was controlled to be completed within 1 hour, ensuring that the reaction temperature did not exceed 0°C. The reaction solution gradually changed to dark yellow color. After 1 hour of reaction, the reaction mixture was slowly poured into a beaker containing 20 g of crushed ice. After the ice was completely melted, it was extracted with dichloromethane (5 x 5 mL). The organic phases were combined, neutralized with 10% sodium bicarbonate solution and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give a yellow needle-like crystal product in quantitative yield (0.23 g). The melting point of the product was 128-130 °C. IR spectrum (KBr pressed sheet, νmax, cm^-1 ): 3050, 3019, 2953, 2918, 2850, 1563, 1486, 1414, 1387, 1351, 1318, 1145, 1045, 831, 807, 755. nmr hydrogen spectrum (500 MHz, CDCl3, δ, ppm): 9.05 (1H, dd, J=4.2, 1.6 Hz, H-2), 8.15 (1H, d, J=9.0 Hz, H-7), 8.05 (1H, d, J=8.6 Hz, H-4), 7.92 (1H, d, J=9.0 Hz, H-8), 7.61 (1H, dd, J=8.6, 4.2 Hz, H-3). NMR carbon spectrum (125 MHz, CDCl3, δ, ppm): 152.1, 146.6, 133.3, 132.9, 129.8, 123.8, 123.4, 121.4, 112.2.Elemental analysis (C9H5BrN2O2) Calculated values (251.95): C, 42.72; H, 1.99; N. 11.07. Measured values: C, 42.54; H, 2.03; N, 11.12.
References
[1] Arkivoc, 2018, vol. 2018, # 3, p. 362 - 374
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 18, p. 8374 - 8389
[3] Patent: WO2008/51808, 2008, A2. Location in patent: Page/Page column 78
[4] Organic Letters, 2016, vol. 18, # 18, p. 4750 - 4753
[5] Chemische Berichte, 1882, vol. 15, p. 1910
